PROJECT SUMMARY Tobacco use remains the leading preventable cause of death and illness in our society, and smoking rates are disproportionately high among people living with HIV. NCI, nicotine dependence researchers, and HIV clinicians have all called for research to evaluate targeted and tailored smoking cessation programs for smokers living with HIV (SLWH), leading to the current request for applications (RFA-CA-18-027). Research suggests SLWH are largely unaware of the HIV-specific deleterious effects of smoking and often lack motivation and confidence in their ability to quit. For these reasons, we developed the Wellness Intervention for Smokers with HIV (WISH). WISH is grounded in the Information-Motivation-Behavioral Skills (IMB) Model and delivered remotely by mobile phone (voice and text message). The program is designed for all SLWH, regardless of their initial motivation to quit. WISH follows evidence-based, best practice guidelines for nicotine dependence treatment, but is innovative in its use of a more comprehensive wellness approach. That is, the intervention addresses both smoking and a number of other personally relevant health behaviors (such as treatment adherence, stress/mood, nutrition, other substance use, etc.), making it relevant and engaging to all SLWH, not just those ready to stop smoking. For those not yet ready to quit, WISH is designed to build and strengthen motivation and self-efficacy for quitting, while smokers also work on other personal health goals. Once ready to quit smoking, participants receive evidence-based cognitive-behavioral counseling and encouragement to use nicotine replacement therapy (NRT) or other appropriate pharmacotherapy. WISH builds on our extensive experience creating motivationally-enhanced cessation interventions and has been pilot tested with SLWH. In this trial, we will compare the effectiveness of WISH to standard care services offered through the National VA Quitline and the SmokefreeVET texting program, NCI-supported tobacco cessation services available to all Veterans. Participants in both arms can receive phone/ text counseling and have access to pharmacotherapy through VA. Primary outcomes will be biochemically confirmed 7-day point prevalence smoking abstinence and presence of any 24-hour intentional quit attempts. Secondary outcomes will include prolonged abstinence, change in cigarettes per day, intermediate change process outcomes based on the IMB model, as well as metrics of intervention reach and implementation. Consistent with RFA goals, we will also describe comorbidities and explore intervention impact on markers of immune status and mortality risk using the outstanding clinical data resources available through the Veterans Aging Cohort Study (VACS). If effective, WISH could meaningfully reduce smoking among HIV+ Veterans nationwide. To support this goal, dissemination efforts are planned in Year 5 to share the WISH program with the National VA Quitline. Because VA is the largest U.S. provider of HIV care, this research has the potential for significant public health impact.